In vivo functions of CD 44

术语CD 44表示由一个独特基因编码的跨膜蛋白家族。由于10个“变体”外显子的选择性剪接，该家族在蛋白质结构上表现出很大的变异性。CD 44家族成员在正常胚胎发育如肢体形成、免疫应答和造血中起重要作用，并且参与病理过程如致癌性转化、肿瘤转移和自身免疫性疾病。CD 44蛋白的细胞外构象和细胞外性质受到细胞内剪接调节、糖基化、胞质尾区磷酸化以及胞质尾区与细胞内蛋白相互作用的影响。细胞外部分用于与其他细胞或ECM相互作用，从而介导由外向内的信号传导并影响细胞内蛋白（例如ezrin或merlin）的活性。基于我们以前的工作，我们请求支持以下目标：i）ezrin和merlin对细胞生长的调节，这两种蛋白似乎都与CD 44相互作用。ii）鉴定参与调节的可变剪接的因素和机制。iii）鉴定在CD 44-/-小鼠中替代CD 44功能的机制。

The term CD44 designates a family of transmembrane proteins encoded by one unique gene. Due to alternative splicing of ten "variant" exons, the family exhibits great variability in protein structure. Members of the CD44 family play important roles in normal embryonic development such as limb formation, in the immune response and in hematopoiesis and are involved in pathological processes such as carcinogenic tansformation, tumor metastasis and autoimmune diseases. The extracellular conformation and therefore the extracellular properties of CD44 proteins are influenced from inside the cell by splice regulation, glycosylation, phosphorylation of the cytoplasmic tail and interactions of the cytoplasmic tail with intracellular proteins. The extracellular portion serves to interact with other cells or with the ECM thereby mediating outside-in signalling and influencing the activity of intracellular proteins, e.g. ezrin or merlin. Based on our previous work we request support for the following goals: i) Regulation of cell growth by ezrin and merlin both of which seem to interact with CD44. ii) Identification of factors and mechanisms that are involved in regulated alternative splicing. iii) Identification of mechanisms substituting for CD44 functions in CD44-/- mice.